Value of original and modified pathological scoring systems for prognostic prediction in paraffin-embedded donor kidney core biopsy

Abstract Background No study has validated, compared and adapted scoring systems for prognosis prediction based on donor kidney core biopsy (CB), with less glomeruli than wedge biopsy. Methods A total of 185 donor kidney CB specimens were reviewed using seven scoring systems. The association between the total score, item scores, score-based grading, and allograft prognosis was investigated. In specimens with less than ten glomeruli (88/185, 47.6%), scoring systems were modified by adjusting weights of the item scores. Results The Maryland aggregate pathology index (MAPI) score-based grading and periglomerular fibrosis (PGF) associated with delayed graft function (DGF) (Grade: OR = 1.59, p < 0.001; PGF: OR = 1.06, p = 0.006). Total score, score-based grading and chronic lesion score in scoring systems associated with one-year and 3-year eGFR after transplantation. Total-score-based models had similar predictive capacities for eGFR in all scoring systems, except MAPI and Ugarte. Score of glomerulosclerosis (GS), interstitial fibrosis (IF), tubular atrophy (TA), and arteriolar hyalinosis (AH) had good eGFR predictive capacities. In specimens with less than ten glomeruli, modified scoring systems had better eGFR predictive capacities than original scoring systems. Conclusions Scoring systems could predict allograft prognosis in paraffin-embedded CB with ten more glomeruli. A simple and pragmatic scoring system should include GS, IF, TA and AH, with weights assigned based on predictive capacity for prognosis. Replacing GS scores with tubulointerstitial scores could significantly improve the predictive capacity of eGFR. The conclusion should be further validated in frozen section.

Figure S2: Comparison of the goodness of fit of linear regression models established in specimens with a glomerular number ≥ 10. (A) One-year eGFR prediction; (B) Three-year eGFR prediction.The item-score-based models predicted eGFR.Score of scar and score of mesangial matrix increase were 0 so that the linear regression models could not be established.The goodness of fit of each model was compared with that of GS score as the reference model, by the Vuong test.Label * would be assigned only if a model differed significantly from the reference model.GS: glomerulosclerosis; IF: interstitial fibrosis; TA: tubular atrophy; CV: chronic vascular change; AH: arteriolar hyaline thickening; TI: total interstitial inflammation; GT: glomerular thrombus; ATI: acute tubular injury; I: interstitial inflammation; PGF: peri-glomerular fibrosis; WLR: wall-lumen ratio.

Figure
Figure S1 eGFR boxplot of recipients in different grades of different scoring systems in specimens with a glomerular number <10.(A) Banff donor scoring system; (B) CADI scoring system; (C) DDS scoring system; (D) MAPI scoring system; (E) Pirani scoring system; (F) Remuzzi scoring system; (G) Ugarte scoring system.FigureS2: Comparison of the goodness of fit of linear regression models established in specimens with a glomerular number ≥ 10. (A) One-year eGFR prediction; (B) Three-year eGFR prediction.The item-score-based models predicted eGFR.Score of scar and score of mesangial matrix increase were 0 so that the linear regression models could not be established.The goodness of fit of each model was compared with that of GS score as the reference model, by the Vuong test.Label * would be assigned only if a model differed significantly from the reference model.GS: glomerulosclerosis; IF: interstitial fibrosis; TA: tubular atrophy; CV: chronic vascular change; AH: arteriolar hyaline thickening; TI: total interstitial inflammation; GT: glomerular thrombus; ATI: acute tubular injury; I: interstitial inflammation; PGF: peri-glomerular fibrosis; WLR: wall-lumen ratio.Figure S3: Comparison of GS score in different scoring systems.(A) Correlation heatmap; (B) Comparison of the goodness of fit of GS-score-based linear regression models in predicting eGFR.The goodness of fit of each model was compared with that of Banff donor scoring system as reference by the Vuong test.Label * would be assigned only if a model differed significantly from the reference model.GS: glomerulosclerosis.FigureS4Comparison of allograft prognosis in specimens with a glomerular number ＜ 10, stratified across each modified scoring system predefined risk groups.(A) Banff donor scoring system; (B) CADI scoring system; (C) DDS scoring system; (D) MAPI scoring system; (E) Pirani scoring system; (F) Remuzzi scoring system

Figure S3 :
Figure S1 eGFR boxplot of recipients in different grades of different scoring systems in specimens with a glomerular number <10.(A) Banff donor scoring system; (B) CADI scoring system; (C) DDS scoring system; (D) MAPI scoring system; (E) Pirani scoring system; (F) Remuzzi scoring system; (G) Ugarte scoring system.FigureS2: Comparison of the goodness of fit of linear regression models established in specimens with a glomerular number ≥ 10. (A) One-year eGFR prediction; (B) Three-year eGFR prediction.The item-score-based models predicted eGFR.Score of scar and score of mesangial matrix increase were 0 so that the linear regression models could not be established.The goodness of fit of each model was compared with that of GS score as the reference model, by the Vuong test.Label * would be assigned only if a model differed significantly from the reference model.GS: glomerulosclerosis; IF: interstitial fibrosis; TA: tubular atrophy; CV: chronic vascular change; AH: arteriolar hyaline thickening; TI: total interstitial inflammation; GT: glomerular thrombus; ATI: acute tubular injury; I: interstitial inflammation; PGF: peri-glomerular fibrosis; WLR: wall-lumen ratio.Figure S3: Comparison of GS score in different scoring systems.(A) Correlation heatmap; (B) Comparison of the goodness of fit of GS-score-based linear regression models in predicting eGFR.The goodness of fit of each model was compared with that of Banff donor scoring system as reference by the Vuong test.Label * would be assigned only if a model differed significantly from the reference model.GS: glomerulosclerosis.FigureS4Comparison of allograft prognosis in specimens with a glomerular number ＜ 10, stratified across each modified scoring system predefined risk groups.(A) Banff donor scoring system; (B) CADI scoring system; (C) DDS scoring system; (D) MAPI scoring system; (E) Pirani scoring system; (F) Remuzzi scoring system but none of the following abnormalities； 2: ≥ 10%GS, Moderate-Severe fibrosis, Tubular Atrophy, Hypertensive arteriolopathy, hyaline change AH: arteriolar hyaline thickening; CV: chronic vascular change (Arterial intimal fibrosis); WLR: wall-lumen ratio; PGF: peri-glomerular fibrosis * Scored by percentage of narrowing of vascular lumen ** Mild: <10% of capillaries occluded; Moderate: 10-25% occlusion; Severe: >25% occlusion † Mild: epithelial fattening, tubule dilation, nuclear dropout, loss of brush border; Moderate: focal coagulative type necrosis; Severe: infarction.

Table S1
Scoring criteria of different scoring systems

Table S2
Comparison of the demographical and clinical characteristics between allografts enrolled and without PTDB.